Elimination of only one type of inhibitory receptor with even a weak inhibitory potential may therefore not be sufficient to detectably alter their functional activity. It

is also possible that the loss of KLRG1 in NK or T cells is compensated by altered expression of other cell surface recognition structures. The observed increased reactivity of NK cells from KLRG1 KO mice toward E-cadherin-transfected target cells was unexpected. Besides KLRG1, there is only one additional receptor, αEβ7 (CD103), known to be expressed on lymphocytes that can bind E-cadherin 35. However, the NK cells used in our experiments did not express CD103 (data not shown). In addition to its adhesive role, E-cadherin is also involved in the Wnt signaling pathway by sequestering β-catenin and is also known INCB024360 to inhibit the ligand activation of receptor tyrosine kinases 36. Thus, it is possible that ectopic expression of E-cadherin in K562 cells alters click here the expression of other yet undefined cell surface molecules that may play a role in NK-cell recognition. KLRG1 expression has been associated with distinct stages during NK and T-cell differentiation and differences between KLRG1+ and KLRG1− lymphocytes subsets have been demonstrated in several instances. This includes the decreased ability of MCMV-activated KLRG1+ NK cells to produce IFN-γ 21, the low level of KLRG1 expression by non-responsive NK cells lacking self-MHC-specific

inhibitory receptors 20, 37, the impaired capacity of KLRG1+ effector/memory T cells to proliferate 7, 11, 13, 14, 29, the paucity of KLRG1+ effector/memory cells to produce IL-2 and inability Carnitine palmitoyltransferase II of KLRG1+ effector cells to give raise to long-lived memory T cells 15, 16. Importantly, the experiments performed here revealed

that KLRG1 serves as marker for these lymphocyte differentiation stages and their functional characteristics but it does not play a deterministic role. Of note, treatment of B6 mice with anti-KLRG1 mAb did also not affect induction of LCMV-specific CD8+ T cells determined by MHC class I tetramer staining and did also not influence the extent of CD62L- and CD127-downregulation in these cells during the acute phase of the infection (data not shown). Even though our study did not reveal alterations of immune functions in the absence of KLRG1, we certainly cannot exclude the possibility that KLRG1 regulates T-cell or NK-cell functions that we have not investigated in this first characterization of these mice. We have recently observed that KLRG1-E-cadherin binding can also strengthen the interaction between cells 26. Thus, the effect of KLRG1 deficiency on lymphocyte adhesion in epithelial tissues expressing E-cadherin such as lung, intestine or skin will have to be tested. In addition, autoimmune models in which slightly activated lymphocytes persist in such tissues could now be used together with the KLRG1-deficient mice generated here.

hawaiiensis, using an experimental model of disseminated infection in immunocompromised

mice. Several inocula were tested over a range 1 × 103–1 × 106 colony-forming units/animal. Both species had a similar behaviour, producing Pexidartinib clinical trial a high mortality. Tissue burden and histopathology studies demonstrated that lung was the organ most affected. “
“Managing fungal diseases remains a major challenge for clinicians despite the improved armamentarium of antifungal agents. This review identified 19 publications reporting safety data on micafungin. Two of these publications were spin off publications, the remaining 17 (15 prospective, two retrospective) were included in the main assessment. Major adverse events reported which occurred in more than 2% in the study populations were infusion-related, gastro-intestinal and hepatic selleck kinase inhibitor (LFT parameters elevations). Micafungin demonstrated significantly less renal events compared with liposomal amphotericin

B and less hepatic events compared with voriconazole. Compared with fluconazole no significant treatment-related adverse events were found except one trial reporting significantly less somnolence but more chills. Micafungin has a similar favourable safety profile in comparison with other echinocandins or fluconazole. “
“Invasive fungal infections (IFIs) are associated with high morbidity and mortality in immunocompromised patients. Although Aspergillus spp. remain an important cause of IFI, other moulds such as Fusarium spp., dematiaceous fungi and Mucorales have become increasingly prevalent among this patient population. Diagnosis and treatment of invasive mould infections remain a challenge. Because of the poor prognosis associated with IFIs, understanding the activity, efficacy and limitations of the available drugs is critical to select the appropriate antifungal agent on an individualised basis. “
“The genus Spiromastix consists of several fungal species that have been isolated from soil and animal dung in various parts of the world. However, these species are considered see more to be of low pathogenic potential, as no cases of infections

caused by these fungi have been reported. Here, we describe the clinical course of discospondylitis in a dog from which a fungus was cultured from a biopsy and identified as a Spiromastix species by morphologic characteristics and sequencing. Phylogenetic analysis determined this to be a new species, Spiromastix asexualis, which is described, and a new order, Spiromastixales, is proposed. “
“The study was performed to analyse the spectrum of dermatomycoses in southwest Poland during the period 2003–2007. A total of 10 486 patients were investigated for fungal skin infections by means of native specimen and cultivating procedures. Skin scrapings, plucked hairs and nail clippings were examined and identified by direct microscopy and culture.

TNF polymorphism rs1800630 A-allele was associated with lower specific anti-pneumococcal IgG levels compared with children carrying C/C genotype of rs1800630. Typhoid fever.  Typhoid fever is caused by Salmonella enterica infection with serotype Typhi and 22 million cases of typhoid fever occur worldwide per year, resulting in 200,000 deaths. Indonesian study suggested a protective role of DRB1*12021 for complicated typhoid fever. Keuter et al. [43] found https://www.selleckchem.com/products/chir-99021-ct99021-hcl.html a lower level of TNF-α in the patients with acute phase of typhoid fever than in convalescence. The seven polymorphisms have been found within the genes BAT1 (a member of the DEAD-box

protein family encoding an ATP-dependent RNA helicase and a negative regulator of inflammation), LTA and TNF. All three genes, or haplotypes spanning these genes, have been associated with a variety of infectious and inflammatory diseases. Dunstan et al. [44] genotyped eighty SNPs in a region of 150 kb in Vietnamese individuals.

Thirty-three SNPs with a minor allele frequency of greater than 4.3% were used to construct haplotypes. Fifteen SNPs which tagged the 42 constructed haplotypes were selected. The haplotype-tagging SNPs (T1–T15) were genotyped, and allelic frequencies of seven SNPs (T1, T2, T3, T5, T6, T7 and T8) have shown a significant difference between typhoid cases and controls. Haplotype-based analysis of the tag SNPs provided positive evidence of association find more with typhoid. The analysis detected a low-risk cluster of haplotypes that each carries the minor allele of T1 or T7, but not both, and otherwise carries the combination of alleles *12122*1111 at T1–T11. Individuals who carry the typhoid fever–protective haplotype *12122*1111 also produce a relatively low TNF-α response to LPS. Severe sepsis in trauma patients.  In the non-coronary intensive care unit, sepsis is the prevalent cause of death. A restriction fragment length polymorphism (RFLP) present in TNF gene is correlated

with increased level of TNF-α in plasma and a high mortality rate in patients with severe sepsis. This non-synonimous polymorphism in the first intron of the TNF-β gene (1064–1069 position) is responsible Nintedanib (BIBF 1120) for an amino acid change at position 26 (asparagine for the TNFB1 sequence and threonine for the TNFB2 sequence) [45]. Previously, the mortality rate in severe sepsis was found to be significantly increased in patients homozygous for the allele TNFB2 of the Nco1 polymorphism compared with heterozygous patients [46]. A statistically highly significant association was obtained between the genotype of the biallelic Nco1 polymorphism of the TNF β gene and the development of severe sepsis after severe blunt trauma. Subjects homozygous for the allele TNFB2 have a significantly increased risk of the development of severe post-traumatic sepsis.

The Congress was attended by over 600 participants representing 31 countries with the bulk coming from the various states of India. A special effort was made to encourage the participation of young immunologists and post doctoral scientists

by providing them bursary support and a platform for competitive presentation. The Congress was held in Hotel Le Meridien which provided an excellent scientific ambience. Situated in the heart of Delhi, very close to the historical monuments, and with the weather turning out to be brilliant, the week-long activity was a perfect blend of high science Selleckchem BI 6727 and social interaction. The Congress format was organized into 10 master lectures delivered by experienced

researchers, nine theme-based symposia with 54 invited speakers and six parallel workshop sessions featuring 65 oral presentations selected from over 400 submitted abstracts. In addition, there were two dedicated poster review sessions. The program covered a wide range of important topics that included the immunological basis of autoimmune and infectious diseases including HIV and type Target Selective Inhibitor Library chemical structure 1 diabetes, cross talk between innate and adaptive immunity, immunodeficiencies, issues related to organ and bone marrow transplantation, immunological tolerance, tumor immunology, stem cells and regenerative medicine and new developments towards vaccine, immune diagnostics and cell therapy. The organizing committee introduced e-poster presentation at this Congress as an effective means of promoting these peer networking and healthy discussion. Twelve

computer stations were provided and these displayed the submitted posters in 3–4 screen pages each. The participants had the opportunity to view, at their convenience, the allotted posters of each day on big screens by clicking the poster number of interest; this also facilitated the discussion of the data with others and with the poster judges. Six best posters (2 for each day of the Congress) were awarded a cash prize and certificate during the valedictory ceremony. The awards were made available through a small grant from International Immunology (facilitated by the Editor-in-chief, Tadamitsu Kishimoto), which is published by Oxford University Press, on behalf of the Japanese Society for Immunology. An important highlight of the Congress was the session ‘Ten best oral presentations’, the participants of which were selected by a panel of international experts. Several awards were instituted to recognize the hard work put in by young researchers, with the ultimate goal being to promote excellence in research. Another important feature of the Congress was the ‘Round Table discussion’ session highlighting the issues related to ‘Gender equality and career development’.

Thereafter, 100 μL of rabbit anti-goat IgG–HRP conjugate (1 : 3000 dilutions) was added. The plate was kept at room temperature for 90 min. The unbound conjugate was removed, and the wells were washed as before. Freshly prepared OPD (100 μL/well) was added, and the reaction was stopped after 5 min by adding 100 μL of 2·5 m H2SO4. The absorbance was measured at 490 nm in a Bio-Rad Model 680 microplate reader. The effect of H.c-C3BP on complement activity was measured by determining the lysis of sensitized sheep erythrocytes and formation of membrane attack complex (MAC). The erythrocyte lysis was determined essentially as described earlier [17] by measuring the release of haemoglobin at 415 nm from

ruptured erythrocytes due to complement this website action. In brief, sheep blood was collected in acid citrate and centrifuged at 400 g for 10 min (Remi

R8C, Remi Sales and Engineering Ltd., Mumbai, India). The plasma and buffy coat layer were discarded, and the packed RBCs were washed three times with normal saline. One volume of saline-washed RBC was mixed with one volume of 1 : 250 diluted decomplemented (at 56°C for 30 min) rabbit anti-sheep RBC antiserum (a kind gift from Dr. Tapas Goswami, Immunology Section, IVRI, Izatnagar) and incubated at 37°C for 30 min. The sensitized cells were washed three times with normal saline, with centrifugation at 400 g for 10 min. After the final wash, 2% cell suspension was prepared with saline containing 1 mm CaCl2. In initial experiments, 25 μL of normal rabbit serum gave appreciable cell lysis and was chosen for the assay. GSK126 The sensitized cells (100 μL) were incubated with 25 μL C-X-C chemokine receptor type 7 (CXCR-7) rabbit

serum in a total volume of 200 μL prepared with saline–calcium for an hour and further at 4°C for at least 4 h. For assessing the effect of H.c-C3BP, varying concentrations of protein were added to rabbit serum in saline–calcium and incubated at 4°C for an hour, followed by the addition of sensitized cells and further incubation. Control wells in triplicate with no serum, no protein, but 100 μL of saline–calcium and cells were included as negative control. Positive control wells had 100 μL of distilled water and cells. After incubation, 150 μL of the supernatant from each well was carefully aspirated and transferred to wells of a flat-bottomed microtitre plate, and the optical absorbance was measured at 415 nm. The effect of H.c-C3BP on complement C3 activation (MAC formation) was studied with modifications of earlier method [18]. The wells of a microtitre plate were coated with 100 μL of 10 μg/mL LPS in carbonate–bicarbonate buffer (100 mm, pH 9·6) and incubated at 4°C overnight. After washings, 100 μL of denatured gelatin in PBS was added and kept at room temperature for 90 min. After washings, 100 μL of fresh goat serum (1%) diluted in 10 mm Tris (pH 7·4) and 120 mm NaCl containing varying concentrations of H.c-C3BP (3·125–12·5 μg/mL) was added. The serum–H.

Tetracycline-mediated inhibition of de novo bacterial protein synthesis promotes the loss of ubiquitinated proteins from the AVM. This effect is reversible, as removal of tetracycline restores AVM ubiquitination to pretreatment levels. These results demonstrate a novel mechanism

by which A. phagocytophilum remodels the composition of its host cell-derived vacuolar membrane and present the first example of a Rickettsiales pathogen co-opting ubiquitin during intracellular residence. Anaplasma VEGFR inhibitor phagocytophilum is a tick-transmitted obligate intracellular bacterium that infects neutrophils to cause the emerging and acute febrile infection, human granulocytic anaplasmosis (HGA) (Chen et al., 1994; Rikihisa, 2011). In nature, A. phagocytophilum is maintained in an enzootic cycle between its tick vector and mammalian hosts. Humans are accidental hosts. HGA clinical manifestations range in severity from asymptomatic to severe disease and death. Although often self-limiting, severe complications such as prolonged fever, shock, leucopenia, thrombocytopenia, high levels of C-reactive protein

and hepatic transaminases, pneumonitis, acute renal failure, and hemorrhages can result. Doxycycline is the drug of choice for treating HGA (Thomas et al., 2009). Following entry, A. phagocytophilum facilitates survival by replicating exclusively within a host cell-derived vacuole that exhibits altered Lumacaftor in vitro fusogenicity. The A. phagocytophilum-occupied Calpain vacuole (ApV) does not mature along the endosomal pathway, does not acidify, avoids lysosomal fusion, and prevents bacterial exposure to reactive oxygen species by avoiding fusion with secretory vesicles and specific granules harboring

NADPH oxidase (Webster et al., 1998; Gokce et al., 1999; Mott et al., 1999; Carlyon et al., 2004; IJdo & Mueller, 2004; Huang et al., 2010a). The ApV is not an inert compartment that is completely sequestered from interfacing with its host cell. Rather, it co-opts membrane traffic, host cell molecules, and cellular processes to camouflage itself and obtain requisite nutrients. For example, the ApV selectively recruits recycling endosome-associated Rab GTPases while excluding Rabs that would otherwise direct A. phagocytophilum to the lysosome (Huang et al., 2010a, b, c). Also, the ApV membrane (AVM) has been shown to accumulate early autophagosomal markers, caveolae markers, and cholesterol, each of which is important for bacterial survival, as well as multiple signaling molecules (Lin & Rikihisa, 2003a, b; Niu et al., 2008). These phenomena serve as harbingers that the A. phagocytophilum likely hijacks additional host cell molecules as part of its intracellular survival strategy. Post-translational modification by ubiquitin is a highly conserved eukaryotic cell-specific process. Ubiquitin is a 76 amino acid protein that is covalently attached to lysine residues of target proteins.

11). Four patients (nos 3, 4, 6, 8) had no detectable vulvar lesion after a recent treatment. The lesion surfaces in the other 12 patients

ranged between 0·5 and 20 cm2 (mean 4·1 cm2 ± 2·6 cm2). In accordance with the Ethics Committee of Cochin hospital, 150 ml blood samples were collected the day of entry in the study in every patient after informed consent. In most cases, blood samples were collected further every 6 months for 12 or 18 months. Peripheral blood mononuclear buy CHIR-99021 cells (PBMC) were isolated by centrifugation through lymphocyte separation medium (Pharmacia, Uppsala, Sweden) and either used immediately or frozen with 10% dimethylsulphoxide (DMSO) and stored at −180°C in liquid nitrogen. HPV-16 typing was performed by polymerase chain reaction (PCR) with DNA extracted from keratinocytes followed by restriction mapping of the amplified products. Multiplex PCR was performed using specific E6 HPV-16 and HPV-18 primers, as described mTOR inhibitor previously [25]. HeLa and SiHa cell lines were used as negative and positive controls, respectively. After 40 cycles of amplification, products were analysed on 5% polyacrylamide gels. When a HPV DNA band was detected, the amplified product was digested with restriction enzymes.

The appropriate restriction pattern of amplified products, together with its size, confers virtually 100% specificity on the PCR reaction. Eighteen overlapping peptides (15-mer to 24-mer) spanning the entire length of the E6 and E7 proteins (Table 2) were synthesized by Neosystem (Strasbourg, ID-8 France). Twelve short peptides (8–10 amino acids) included into E6/2 (14–34) and E6/4 (45–68) large peptides selected on the basis of the presence of known motifs of binding to different HLA class I molecules were synthesized by Chiron Mimotopes (Emeryville, CA, USA). PBMC (2 × 105/200 µl) were cultured in

96-well round-bottomed microtitre plates in complete medium with individual antigenic peptides in triplicate. After 5 days of culture, 1 µCi of [3H]-TdR (NEN, Paris, France) was added to each well for 18 h. Cells were harvested using an automatic cell harvester (Skatron, Sterling, VA, USA) and [3H]-thymidine incorporation was quantified by scintillation counting. Proliferative responses with a stimulation index [SI = counts per minute (cpm) in the presence of antigen/cpm in control media which must be higher than 500 cpm] above 3 were scored as positive. ELISPOT–IFN-γ assays were performed as described previously [26]. Briefly, nitrocellulose plates (Multi-Screen HA; Millipore, Bedford, MA, USA) were coated overnight at +4°C with 0·1 µg of mouse anti-human IFN-γ monoclonal antibody (mAb) (Genzyme, Russelheim, Germany).

Another meta-analysis, by Boudville et al. examined the effect of donation on blood pressure.29 This concluded that donors may have a 5 mmHg increase in blood pressure within 5–10 years of donation. Ibrahim et al. assessed the vital status and lifetime risk of end-stage kidney disease (ESKD), GFR, urinary albumin excretion, prevalence of hypertension, general health status and quality of life in 3698 kidney donors.30 Survival and risk of ESKD was not significantly different to those in the general population. Most donors had a preserved GFR, normal albumin excretion and an excellent quality of life. It is important to point out that the absence

of any large prospective, well-controlled, long-term follow-up studies on live donors is seen as a significant deficiency.27,31,32 Furthermore, long-term studies regarding live donors with isolated Talazoparib abnormalities (e.g. hyperlipidaemia, mild hypertension, obesity) selleck inhibitor are also lacking, and the long-term risks in these subjects remain particularly ill defined. It is hoped that the recently established ANZDATA Live Donor Registry will help in further

clarifying the true long-term donor outcomes in Australia and New Zealand. With regards to the short-term risks, these are predominantly related to the surgical procedure. The risk of perioperative mortality is generally regarded as being approximately 1 in 3000 – a figure derived from large American surveys33 and several Mannose-binding protein-associated serine protease single centre reports. Although Australian and New Zealand registry data are currently lacking, of approximately 5000 live kidney donations that have occurred in Australia and New Zealand to date, the transplant community is currently aware of two perioperative deaths (anecdotal reports). The risk of non-fatal major perioperative complication is also generally felt to be low, approximating 2–4% in most published series (see later subtopics for a detailed account of the supporting literature). The majority of these complications have been haemorrhagic episodes, although a variety of other events have been reported including

bowel obstruction, bowel injury, thromboembolic events, pneumothoraces, hernia development and rhabdomyolysis. Prasad et al. performed an observational cohort study of 58 living donors to 6 months post-donation for changes in 24 h ambulatory blood pressure profile, kidney function, urine protein excretion, body mass index, glucose intolerance and fasting lipid profiles.34 No significant changes in blood pressure, protein excretion, body mass index, glucose and lipids were found. Estimated glomerular filtration rate declined significantly (P < 0.0001). Most of the data presented here comes from Registries and from large retrospective cohort studies. There is a lack of prospective long-term data regarding live donor safety, particularly in relation to consequences of donation in certain donor subgroups.

The injected dye was mostly located in the hippocampus

CA1–3 region when injection time was longer PXD101 cost than 30 min (Supporting Information Fig. 4). In the water maze assessment, LPS injection resulted in neurologic deterioration at 3 days, with little improvement for up to 21 days. This deterioration of neurological function was restored by IL-13 injection (Fig. 6B and Supporting Information Fig. 5). Furthermore, injection of IL-13-neutralized antibody caused a similar neurologic outcome as that of the LPS group. Injection of IL-13 did not cause significant neurologic dysfunction compared with the PBS group. On the day of the worst neurologic dysfunction (3 days after stereotactic injection), the brain was harvested to assess the distribution of microglial/monocyte and neuronal survival (Fig. 6). LPS injection increased the deposition of CD11b with a reciprocal decrease in NeuN-positive

cells. Co-injection of LPS with IL-13 SB203580 decreased the number of CD11b positive cells and further restored the number of NeuN positive cells. Ablation of IL-13 with IL-13 NA exerted the same effect as LPS injection. LPS injection increased the expression of C/EBP-α and C/EBP-β in CD11b positive cells, while the combination of LPS and IL-13 only caused the expression of C/EBP-α in CD11b positive cells. The combined effect of LPS and IL-13 in C/EBP-α and C/EBP-β was abolished by IL-13 NA. Hence, microglia/macrophage (CD11b positive cells) was activated by LPS injection and IL-13 further aggravated the microglia/macrophage cell loss. Attenuation of microglia/macrophage cells increased the number of neuronal cells and provided a more favorable neuro-behavioral response in animals. A previous study reported that IL-13-enhanced ER stress-related calpain activation plays an important role in the downregulation of PPAR-γ-regulated

HO-1 expression in activated microglia. The present study shows that IL-13 enhances COX-2/PGE2 expression through PLA2 and C/EBP-α regulation. More importantly, IL-13 simultaneously augments ER stress and calpain activity, and cleavage of C/EBP-β and PPAR-γ expression results in aggravation of activated microglia death. Morin Hydrate Finally, this study is the first to demonstrate that administration of IL-13 in activated microglia in an animal model enhances C/EBP-α expression, but abolished C/EBP-β expression, which diminishes neuronal cell loss and damage in regions associated with memory and the hippocampal CA3 region. The ER is a major component of the protein quality control system. Emerging evidence indicates a potent association between accumulation of protein aggregates and ER stress induction in various important neurodegenerative conditions. Previous reports have shown that calpain inhibitors have impressive neuroprotective effects in in vivo models of cerebral ischemia.

However, minor, albeit significant, changes were observed in the percentage of pre-marginal zone, marginal zone, T2 and B1 B cells. Although the

meaning of this observation is presently unclear, this finding suggests that Treg cells may also contribute to maintaining overall homeostasis of splenic B-cell populations. In addition to disrupting Treg-cell activity Trichostatin A order with administration of anti-GITR mAb, a large number of studies have examined the role of Treg cells in immune responses using a depleting anti-CD25 mAb.51–55 High-dose anti-CD25 treatment deletes most but not all Treg cells, because a minority of Foxp3+ T cells in secondary lymphoid tissues are CD25.1–47,52 BALB/c mice were injected with 250 μg of either anti-CD25 mAb (PC61) or control rIgG on days −2, +1, +5 with injections continued twice weekly until the mice were killed. Mice were immunized with SRBC on day 0 and splenic GCs were examined on days 8–24. As opposed to continuous anti-GITR mAb treatment, extended anti-CD25 mAb treatment did not lead to mortality, probably because of the protective activity of residual CD25− Treg cells. Similar to mice treated with anti-GITR mAb, however, injection of anti-CD25 mAb resulted in a larger total GC response and a progressive imbalance

of switched to IgM+ GC B cells (see Supplementary material, Fig. S2). Regardless of the means by which Treg-cell activity was inactivated, therefore, GC responses were markedly dysregulated. Although both anti-GITR mAb and anti-CD25 mAb treatments are well Vincristine datasheet accepted methods for inactivating Treg cells in vivo, it is possible that the mAbs may have direct effects on GC B cells. To rule out this possibility, GC B cells were tested at days 8, 12 and 18 post-immunization for expression of GITR and CD25. As shown in Supplementary material, Fig. S3, GC B cells were negative for these molecules at all time-points tested.

To ensure that Treg-cell control of GC responses was strain independent, C57BL/6 mice were similarly challenged with SRBC and treated with either anti-GITR mAb or control Thalidomide rIgG (Fig. 2). Even though control-treated C57BL/6 mice generated a smaller splenic GC reaction after SRBC immunization compared with BALB/c mice (Fig. 2a,b), the response was again characterized by a steady ratio of IgM+ to switched B cells at all time-points (Fig. 2c). Importantly, anti-GITR mAb administration resulted in a larger proportion and total number of GC B cells (Fig. 2b), especially at the early time-points, and a disproportionate percentage and number of switched GC B cells throughout the response (Fig. 2c). Similar to findings in BALB/c mice, there was also a significant increase in the percentage of IgG1+ GC B cells at day 8 in anti-GITR mAb compared with rIgG-treated mice (data not shown).